title: Large oncosomes mediate intercellular transfer of functional microRNA.
abstract: Prostate cancer cells release atypically large extracellular vesicles (EVs), termed large oncosomes, which may play a role in the tumor microenvironment by transporting bioactive molecules across tissue spaces and through the blood stream. In this study, we applied a novel method for selective isolation of large oncosomes applicable to human platelet-poor plasma, where the presence of caveolin-1-positive large oncosomes identified patients with metastatic disease. This procedure was also used to validate results of a miRNA array performed on heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct classes of miRNAs are expressed at higher levels in EVs derived from the tumorigenic cells in comparison to their non-tumorigenic counterpart. Large oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect that was increased by miR-1227, a miRNA abundant in large oncosomes produced by RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report metastatic disease in patients with prostate cancer, and that this class of EV harbors functional molecules that may play a role in conditioning the tumor microenvironment.
authors.affiliation: Cancer Biology Program; Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles, CA USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Morello
authors.forename: Valentina R
authors.initials: VR
authors.lastname: Minciacchi
authors.forename: Paola
authors.initials: P
authors.lastname: de Candia
authors.forename: Julie
authors.initials: J
authors.lastname: Yang
authors.forename: Edwin
authors.initials: E
authors.lastname: Posadas
authors.forename: Hyung
authors.initials: H
authors.lastname: Kim
authors.forename: Duncan
authors.initials: D
authors.lastname: Griffiths
authors.forename: Neil
authors.initials: N
authors.lastname: Bhowmick
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Paolo
authors.initials: P
authors.lastname: Gandellini
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
mesh_terms: D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D053263:Gene Regulatory Networks; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034443:RNA Transport; D059016:Tumor Microenvironment
chemical_list: D051242:Caveolin 1; C576906:MIRN1228 microRNA, human; D035683:MicroRNAs
keywords: amoeboid blebbing; exosome; extracellular vesicles; filtration; large oncosome; miRNA; microvesicle; prostate cancer